ABSTRACT The Clinical and Biomarkers Core is critical for the studies in this program project renewal proposal. The Core will recruit smokers to collect biological samples and will carry out analyses of tobacco constituent biomarkers. The biological samples collected by the Core will be used to evaluate and compare biomarkers of tobacco exposure across Japanese Americans, Whites, and Native Hawaiians in Projects 2, 3, and 4. Biomarkers to be analyzed by the Core include total nicotine equivalents (nicotine intake), 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol (NNAL) and its N- and O-glucuronides (exposure to tobacco-specific lung carcinogen NNK), phenanthrene tetraol and 3-hydroxy phenanthrene (exposure to and metabolism of the representative polycyclic aromatic hydrocarbon phenanthrene), mercapturic acids (exposure to acrolein, crotonaldehyde, and propylene oxide), urinary cadmium, as well as urinary biomarkers and DNA adducts derived from oxidative stress and inflammation. The measurements will be carried out on samples from a total of 6,084 subjects, with some of these samples being analyzed for only a subset of biomarkers. The samples from these subjects will either be procured from the existing bioresposity of the Multiethnic Cohort or obtained from smokers who are recruited by this Core. All assays, except for urinary cadmium, are based on stable-isotope dilution mass spectrometry and all have been analytically validated with respect to accuracy and precision. Personnel in this Core have extensive experience in clinical trials and quantitation of urinary tobacco biomarkers and DNA adducts, and were the first to develop many of the methods that will be used in this program project grant. The biological samples and biomarker results generated by this Core will be used by all projects.